Application of luteolin in preparation of anti-tumor metastasis medicine

Abstract

The invention discloses application of luteolin in preparation of anti-tumor metastasis drugs, relates to the technical field of anti-tumor medicines, and comprises application of luteolin or pharmaceutically acceptable salts and pharmaceutically acceptable carriers thereof in preparation of anti-tumor metastasis drugs, and the tumor is nasopharyngeal carcinoma. According to the application of the luteolin in preparation of the anti-tumor metastasis medicine, proliferation of NPC cells is inhibited through the luteolin, migration and invasion capacity of the NPC cells is reduced, and diffusion and metastasis of tumor cells are reduced; in a pulmonary metastatic tumor model constructed by mouse tail intravenous injection, the luteolin significantly reduces the formation of pulmonary metastatic tumor, and proves that the luteolin also has strong anti-metastasis ability in an in-vivo environment; luteolin inhibits the malignant development of NPC by targeting an I L-6 / JAK / STAT3 signal channel; as a natural compound, luteolin is wide in source and low in toxicity, and has relatively high safety and clinical application potential.

Description

Technical Field

[0001] The present invention relates to anti-tumor medicine technology, and in particular to application of luteolin in the preparation of anti-tumor metastasis medicine. Background Art

[0002] Epithelial-mesenchymal transition (EMT) is a biological process in which epithelial cells transform into mesenchymal cells. This process plays an important role in embryogenesis, wound healing, and the malignant progression of malignant tumors. In the field of oncology, EMT is considered to be a key step for tumor cells to acquire the ability to invade and migrate, which promotes the occurrence, development, and metastasis of tumors. During the EMT process, the connection between cells is remodeled, resulting in reduced adhesion between epithelial cells and the basement membrane, and activating a series of transcriptional programs to promote the transformation of cells into mesenchymal cells. This transformation not only gives tumor cells stronger migration and invasion capabilities, but also increases the tolerance of tumors to clinical treatment.

[0003] As a common malignant tumor of the head and neck, nasopharyngeal carcinoma (NPC) has always been a difficult problem in clinical treatment due to its high invasiveness and metastasis. In recent years, the mechanism of EMT in the malignant progression of NPC has gradually become a research hotspot. Studies have found that NPC cells express a series of markers related to mesenchymal cells, such as N-cadherin, vimentin and fibronectin, during the EMT process, while inhibiting the expression of E-cadherin, thereby losing epithelial cell characteristics and acquiring mesenchymal cell characteristics. In terms of anti-tumor, luteolin (LUTE) has been shown to inhibit proliferation, induce apoptosis and promote autophagy in a variety of tumor cells. However, there is currently a lack of in-depth research on whether luteolin can affect the malignant behavior of NPC cells by regulating EMT. Summary of the invention

[0004] The purpose of the present invention is to provide the use of luteolin in the preparation of anti-tumor metastasis drugs to solve the above-mentioned deficiencies in the prior art.

[0005] In order to achieve the above object, the present invention provides the following technical solution: the use of luteolin or its pharmaceutically acceptable salt and pharmaceutically acceptable carrier in the preparation of anti-tumor metastasis drugs, wherein the structural formula of the luteolin is as follows:

[0006] The tumor is nasopharyngeal carcinoma.

[0007] Furthermore, the luteolin or a pharmaceutically acceptable salt thereof is added with pharmaceutical excipients to prepare a preparation.

[0008] Furthermore, the pharmaceutical excipients include one or more of diluents, excipients, fillers, binders, wetting agents, disintegrants, absorption enhancers, surfactants, adsorption carriers, lubricants, and other excipients.

[0009] Furthermore, the preparation is in the form of tablets, capsules, oral liquids, injections, lyophilized preparations for injection or powder injections.

[0010] Compared with existing technologies, LUTE showed a significant inhibitory effect on the proliferation of NPC cells in in vitro experiments, and the inhibitory effect was concentration-dependent, indicating that LUTE has the potential to enhance the efficacy of anti-tumor drugs; verified by scratch healing test and Transwell test, LUTE can significantly reduce the migration and invasion ability of NPC cells, which is crucial for preventing the spread and metastasis of tumor cells; in the lung metastasis model constructed by mouse tail vein injection, LUTE significantly reduced the formation of lung metastasis, confirming that it also has a strong anti-metastasis ability in vivo, providing a solid experimental basis for clinical application; Western Blot results showed that LUTE inhibited the EMT process by downregulating the expression of metastasis-related proteins such as IL-6, p-JAK, p-STAT3 and N-cadherin, and upregulating the expression of E-cadherin, revealing the specific mechanism by which LUTE inhibits the malignant progression of NPC by targeting the IL-6 / JAK / STAT3 signaling pathway;

[0011] Luteolin is a natural compound with a wide range of sources, low toxicity, high safety and clinical application potential. The application of the present invention will help improve the therapeutic effect of malignant tumors such as nasopharyngeal carcinoma and improve the quality of life of patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present invention. For ordinary technicians in this field, other drawings can also be obtained based on these drawings.

[0013] Figure 1 A schematic diagram of the effect of LUTE on NPC cell proliferation provided by an embodiment of the present invention;

[0014] Figure 2 A schematic diagram showing the effect of LUTE on the migration and invasion ability of NPC cells provided in an embodiment of the present invention;

[0015] Figure 3 A schematic diagram of experimental results of LUTE inhibiting NPC migration provided by an embodiment of the present invention;

[0016] Figure 4 A schematic diagram of the expression of proteins related to the EMT and JAK / STAT3 pathways after LUTE intervention in NPC cells provided in an embodiment of the present invention. DETAILED DESCRIPTION

[0017] In order to enable those skilled in the art to better understand the technical solution of the present invention, the present invention will be further described in detail below with reference to the accompanying drawings.

[0018] Embodiment 1:

[0019] See also Figure 1-Figure 4 , Use of luteolin in the preparation of anti-tumor metastasis drugs, use of luteolin or a pharmaceutically acceptable salt thereof in the preparation of anti-tumor metastasis drugs, the structural formula of luteolin is as follows: The tumor is nasopharyngeal carcinoma.

[0020] The luteolin or a pharmaceutically acceptable salt thereof is added with pharmaceutical excipients to prepare a preparation.

[0021] Pharmaceutical excipients include one or more of diluents, excipients, fillers, binders, wetting agents, disintegrants, absorption enhancers, surfactants, adsorption carriers, lubricants, and other excipients.

[0022] The dosage form of the preparation is tablet, capsule, oral solution, injection, lyophilized injection or powder injection.

[0023] Luteolin or a pharmaceutically acceptable salt thereof inhibits the metastasis of nasopharyngeal carcinoma by targeting the IL-6 / JAK / STAT3 signaling pathway.

[0024] Luteolin or its pharmaceutically acceptable salt can be administered to patients who need such treatment in the form of a composition by oral administration, nasal inhalation, rectal administration or parenteral administration. When used for oral administration, it can be made into conventional solid preparations such as tablets, powders, granules, capsules, etc., and liquid preparations such as water or oil suspensions, etc.; when used for parenteral administration, it can be made into solutions for injection, water or oil suspensions, etc. Various dosage forms of the pharmaceutical composition of the present invention can be prepared according to conventional production methods in the pharmaceutical field. For example, the active ingredient is mixed with one or more carriers and then made into the desired dosage form.

[0025] Embodiment 2:

[0026] See also Figure 1 This embodiment provides a technical solution based on the first embodiment: CCK-8 cell viability detection of the effect of LUTE on the proliferation activity of NPC cells.

[0027] Both 5-8F and HONE1 NPC cells are commonly used cell lines in NPC research. The 5-8F cell line is derived from nasopharyngeal carcinoma and is a substrain of the SUNE-1 cell line. It has high metastasis and tumorigenicity and is an important tool for studying the metastasis mechanism of nasopharyngeal carcinoma. By observing the behavioral changes of 5-8F cells under specific conditions, we can gain a deep understanding of the biological characteristics and metastasis mechanism of nasopharyngeal carcinoma. The HONE1 cell line is also derived from nasopharyngeal carcinoma and is one of the poorly differentiated squamous cell carcinoma cell lines. It has specific biological characteristics and is widely used in in vitro experimental studies of nasopharyngeal carcinoma, especially when comparing the responses of different cell lines to the same treatment. Comparative studies with cell lines such as 5-8F can further reveal the heterogeneity and complexity of nasopharyngeal carcinoma. In research on nasopharyngeal carcinoma, the HONE1 cell line has been used in a variety of experiments, including the study of EMT (epithelial-mesenchymal transition) mechanisms.

[0028] Remove 5-8F and HONE1 cells from the culture flask, wash once with PBS, add an appropriate amount of trypsin for digestion, add complete medium to terminate digestion after digestion, and gently blow to disperse the cells into a single cell suspension. Use a cell counter to count the cell suspension, add the cell suspension to each well of the 96-well plate (i.e., inoculate 5×10 cells per well). 3 The 96-well plate was placed in a 37°C constant temperature incubator for 48 hours to allow the cells to adhere to the wall and resume growth.

[0029] According to the experimental design, a series of luteolin solutions with different concentrations (0, 1, 20, 40, 60, 80 μM) were prepared, the old culture medium in each well was removed, 100 μL of fresh culture medium containing the corresponding concentration of luteolin was added to the experimental wells, and culture was continued in a 37°C constant temperature incubator for 24 h.

[0030] After the incubation, add 10 μL of CCK8 reagent to each well and mix gently to avoid bubbles; then put the 96-well plate back into the 37°C constant temperature incubator and incubate for 1 hour, and use an enzyme reader to detect the absorbance value of each well at a wavelength of 450 nm.

[0031] The control wells were wells with a luteolin solution concentration of 0 μM, and the experimental wells were wells with luteolin solutions of different concentrations added. The absorbance value of the blank well (containing only culture medium and CCK8 reagent, no cells) was set as the background value, and the background value was subtracted from the absorbance values ​​of each experimental well and control well.

[0032] The cell viability was calculated according to the following formula:

[0033]

[0034] The cell inhibition rate was calculated according to the following formula:

[0035] Inhibition rate = 100% - cell survival rate

[0036] The experiment was repeated three times, and the average value was taken to improve the reliability of the data. GraphPad Prism or other statistical software was used to draw the concentration-inhibition rate curve and calculate the IC50 value.

[0037] See also Figure 1 , detected by CCK8 cell activity test, after 24h treatment of 5-8F and HONE1 cells with LUTE at a concentration of 20-100μmol / L, the survival rates of 5-8F and HONE1 cells were significantly inhibited compared with the control group (NC group, 0μmol / L), and the concentration-dependent manner was observed. The calculated IC50 values ​​of LUTE for 5-8F and HONE1 were 34.40μmol / L and 44.32μmol / L, respectively, which were used as the subsequent experimental dosage concentrations. The results showed that LUTE could significantly inhibit the proliferation of NPC cells, and the concentration was dependent on the LUTE concentration.

[0038] Embodiment three:

[0039] See also Figure 2 This embodiment provides a technical solution based on the first embodiment: determining the effect of LUTE on the migration of 5-8F and HONE1 cells: scratch healing test.

[0040] 5-8F and HONE1 cells in the logarithmic growth phase were digested from the culture flask and prepared into single cell suspensions; 60×10 4 The number of cells was inoculated into a six-well plate to ensure uniform distribution; the six-well plate was placed in a cell culture incubator at 37° C. and 5% CO 2 and cultured until the cell confluence was close to 80%.

[0041] Use a sterile 200 μL pipette tip to make a vertical and even scratch on the cell monolayer, ensuring that the scratch width is consistent and passes through the entire well; gently wash 2-3 times with PBS to remove the scratched cell debris, and continue to culture for 48 hours.

[0042] According to the experimental design, LUTE was dissolved in serum-free culture medium to prepare three concentrations of culture medium: 0 μmol / L (NC group, i.e., blank control group), 34.4 μmol / L (5-8F-LUTE treated group), and 45.32 μmol / L (HONE1-LUTE treated group); then, culture medium of corresponding concentration was added to each well, 2 mL per well, to ensure that the drug evenly covered the cells.

[0043] An inverted microscope was used to observe and record cell migration at 0h and 48h after scratching, including changes in scratch width and morphology of the cell migration front. A camera system was used to save representative images for subsequent analysis.

[0044] The scratch width (or unhealed area) at 0 h and 48 h was measured using image analysis software, and the healing degree was calculated using the following formula:

[0045]

[0046] See also Figure 2 A, To determine the effect of LUTE on the migration of 5-8F and HONE1 cells, a scratch healing experiment was performed and observed under a common optical microscope at 0 and 48 h. The results showed that after LUTE acted on 5-8F and HONE1 NPC cells for 48 h, the healing degree of the 5-8F-LUTE treatment group and the HONE1-LUTE treatment group was significantly lower than that of the NC group (P < 0.01, Figure 2 A).

[0047] Embodiment three:

[0048] See also Figure 2 This embodiment provides a technical solution based on the first embodiment: to explore whether LUTE can affect the invasiveness of NPC cells: Transwell assay.

[0049] Take 5-8F HONE1 cells in logarithmic phase and adjust the concentration to 1×10 6 NPC cells were collected from each group after the culture and the concentration was adjusted to 1×10 5 / ml, 200 μL was inoculated in Transwell plate chambers with or without matrigel glue, and cultured for 24 h. Then, the cells were fixed with 90% ethanol and stained with 0.1% crystal violet at room temperature. The number of cells passing through the membrane was observed under an inverted microscope. Five fields of view were randomly selected from the center and surrounding parts of each membrane, and the number of cells passing through the micropores of the polycarbonate membrane was calculated.

[0050] See also Figure 2 B. Transwell experiment results showed that compared with the NC group, LUTE could significantly inhibit the invasion ability of 5-8F and HONE1 cells. The results showed that LUTE exhibited significant anti-metastasis ability in 5-8F and HONE1 cells.

[0051] Embodiment 4:

[0052] See also Figure 3 This embodiment provides a technical solution based on the first embodiment: verify whether LUTE also has the effect of inhibiting NPC metastasis in vivo, and construct a metastatic tumor model through tail vein injection.

[0053] NPC 5-8F cells were cultured in a constant temperature incubator at 37°C and 5% CO2, and the cell growth status was observed and subcultured at appropriate times to maintain cell viability; when the cells grew to an appropriate density, they were grouped. The cells in the LUTE group were treated with 34.40 μmol / L LUTE solution, while the NC group was treated with only an equal volume of culture medium as a control.

[0054] When the cell confluency reaches 30%-40%, transfection is performed with lentivirus carrying the green fluorescent protein (GFP) gene. Lentivirus transfection of the GFP gene is a commonly used molecular biology technique used to express and track GFP in living cells, thereby achieving visualization of cell biological processes. Virus dosage (μL) = (number of cells × MOI value / viral stock titer) / 10 3 , and add 5 μg / mL of infection enhancer Polybrene, which is used to improve the infection efficiency of viruses to cells, especially in gene transfection and virus-mediated cell transfection experiments. 72 hours after transfection, observe GFP expression under an inverted fluorescence microscope.

[0055] Take 5-8F cells stably transfected with GFP in the logarithmic growth phase, wash with PBS, digest with trypsin, and terminate the digestion with complete medium. After digestion, centrifuge at 1200 rpm for 4 min, resuspend the cells after centrifugation, and the cell suspension concentration is 1×10 6 cells / 100 μL;

[0056] Healthy mice aged 4 weeks were selected as experimental subjects. The weight, age and genetic background of these mice should be as consistent as possible to reduce experimental errors. The suspension containing GFP-positive cells was slowly injected into the mice through professional tail vein injection technology. Special care should be taken during the injection process to avoid leakage of the cell suspension or causing unnecessary pain to the mice.

[0057] After injection, the mice are placed in a suitable breeding environment and their health status is regularly observed to ensure that no abnormal reactions occur. After 4 weeks of in vivo colonization and proliferation, GFP-positive cells are expected to form visible fluorescent expression areas in the mouse lungs.

[0058] Finally, the mice were killed after 4 weeks, and the lung tissue was quickly dissected. During the dissection process, care should be taken to maintain the integrity and cleanliness of the lung tissue to avoid contamination or damage. After the removed lung tissue was properly processed, GFP expression was observed under an inverted fluorescence microscope. Under blue light excitation, GFP will emit bright green fluorescence, so that the colonization, distribution range and expression intensity of GFP-positive cells in the mouse lungs can be intuitively judged. This observation will provide an important basis for further analysis of the effects of LUTE intervention factors on biological processes such as cell migration, proliferation and differentiation.

[0059] See also Figure 3 A, After 5-8F cells were transfected in vitro, GFP was stably expressed under an inverted fluorescence microscope, and a metastatic tumor model was established by tail vein injection.

[0060] See also Figure 3 B. The results showed that compared with the control group (NC group), the number of lung metastases in the LUTE group was significantly reduced. This result showed that LUTE could effectively inhibit the formation of lung metastases of NPC cells in mice, further confirming that LUTE could inhibit the metastasis of NPC.

[0061] Embodiment five:

[0062] See also Figure 4 This embodiment provides a technical solution based on the first embodiment: exploring the molecular mechanism of LUTE inhibiting NPC cell metastasis: Western Blot experiment.

[0063] Western Blot experiment, also known as protein blotting (immunoblotting test), is a commonly used experimental method in molecular biology, biochemistry and immunogenetics. It is mainly used to detect the presence of specific proteins in samples, molecular weight and protein-protein interactions, etc. It combines the high resolution of polyacrylamide gel electrophoresis (PAGE) and the specificity of immunochemistry, and can accurately identify and quantify target proteins in complex mixtures. Protein bands can be observed through exposure or imaging equipment, and the expression level of the protein can be quantified.

[0064] The IL-6 / JAK / STAT3 signaling pathway is an important signal transduction pathway in cell biology, mainly involving key molecules such as interleukin-6 (IL-6), Janus kinase (JAK) and signal transducer and activator of transcription 3 (STAT3). This pathway plays an important role in a variety of physiological and pathological processes, including inflammatory response, immune response, cell proliferation and differentiation.

[0065] IL-6 first binds to the IL-6 receptor (IL-6R) on the cell membrane to form a complex; the IL-6 / IL-6R complex further binds to the ubiquitously expressed glycoprotein 130 (gp130), leading to the dimerization of gp130;

[0066] After gp130 dimerizes, it activates the JAK kinases (mainly JAK1 and JAK2) bound to it and causes phosphorylation; the phosphorylated JAK kinases further phosphorylate the tyrosine residues of STAT3 (mainly Y705) to form phosphorylated STAT3; the phosphorylated STAT3 interacts through its SH2 domain to form homo / heterodimers and translocates to the cell nucleus; in the cell nucleus, STAT3 dimers bind to the promoters of target genes and initiate the transcription of specific genes, thereby regulating the physiological and pathological processes of the cell.

[0067] The IL-6 / JAK / STAT3 signaling pathway plays an important role in inflammatory and immune responses, and is involved in regulating the production of inflammatory mediators and the activation of immune cells. The pathway is also involved in cell proliferation and differentiation, and has an important impact on the occurrence and development of tumors. Given the key role of the IL-6 / JAK / STAT3 signaling pathway in a variety of diseases, inhibitors targeting this pathway have become potential drug targets for the treatment of inflammatory diseases, autoimmune diseases, tumors, and other diseases. The following is a brief introduction to proteins related to the IL-6 / JAK / STAT3 signaling pathway:

[0068] IL-6 is a multifunctional cellular inflammatory factor and an important member of the interleukin family. It is a small molecule glycoprotein that is usually produced by fibroblasts, monocytes / macrophages, T lymphocytes, B lymphocytes, epithelial cells, keratinocytes and a variety of tumor cells. IL-6 plays an important role in inflammation, immune regulation, hematopoiesis and tumor development. IL-6 may promote tumor cell proliferation, migration and invasion in nasopharyngeal carcinoma cells by activating the JAK / STAT signaling pathway. In addition, IL-6 may also affect the immune escape and drug resistance of tumor cells by regulating the immune microenvironment.

[0069] JAK is a non-receptor tyrosine protein kinase and a key enzyme in the cytokine receptor signal transduction process. In nasopharyngeal carcinoma cells, JAK may be involved in the signal transduction process of various cytokines, such as IL-6, IL-10, etc. The activation of JAK can further activate downstream STAT transcription factors, thereby regulating the growth, differentiation and apoptosis of tumor cells. In addition, JAK may also affect the progression and metastasis of nasopharyngeal carcinoma by interacting with other signaling pathways.

[0070] p-JAK (phosphorylated JAK) refers to the active form of JAK kinase that is phosphorylated after being stimulated by cytokines and other factors. Phosphorylation is an important marker of JAK kinase activation and a necessary condition for the activation of its downstream signaling pathway. In nasopharyngeal carcinoma cells, the level of p-JAK may reflect the activation state of JAK kinase, thereby affecting the signal transduction and biological behavior of tumor cells.

[0071] STAT3 is an important transcription factor that is widely involved in the signal transduction process of cytokines. When cytokines bind to their receptors, JAK kinase is activated and catalyzes the phosphorylation modification of STAT3 to form p-STAT3. p-STAT3 then enters the cell nucleus, binds to the promoter of the target gene, and regulates the expression of the gene. STAT3 is continuously expressed (i.e., abnormally activated) in nasopharyngeal carcinoma. Its abnormal activation may prolong the survival time of nasopharyngeal carcinoma cells by upregulating the expression of anti-apoptotic genes. In addition, STAT3 may also be involved in the proliferation, migration, invasion, and angiogenesis of nasopharyngeal carcinoma cells.

[0072] p-STAT3 (phosphorylated STAT3) is the active form of STAT3 that is phosphorylated after being stimulated by cytokines and other factors. Phosphorylation is an important marker of STAT3 activation and a key step in its transcriptional regulatory function. In nasopharyngeal carcinoma cells, the level of p-STAT3 may reflect the activation state of STAT3, thereby affecting the proliferation, migration and invasion of tumor cells. Therefore, inhibiting the formation or activity of p-STAT3 may become one of the new strategies for the treatment of nasopharyngeal carcinoma.

[0073] N-cadherin is a calcium-dependent intercellular adhesion molecule and a member of the cadherin family. It plays an important role in embryonic development, tissue formation, and cell migration. N-cadherin may be involved in the invasion and metastasis of tumor cells in nasopharyngeal carcinoma. By promoting the adhesion of tumor cells to the extracellular matrix and the interaction between tumor cells, N-cadherin may enhance the migration and invasion ability of nasopharyngeal carcinoma cells. In addition, N-cadherin may further promote the progression and metastasis of nasopharyngeal carcinoma by activating related signaling pathways (such as the PI3K / Akt signaling pathway).

[0074] E-cadherin (E-cadherin) is an epithelial cell-specific calcium-dependent intercellular adhesion molecule and an important member of the cadherin family. It plays a key role in maintaining the morphology, polarity and integrity of epithelial cells. In nasopharyngeal carcinoma, the expression of E-cadherin is often downregulated or absent, which may lead to weakened adhesion between tumor cells, thereby enhancing the invasion and metastasis of tumor cells. In addition, the downregulation or absence of E-cadherin may also affect processes such as tumor cell proliferation and apoptosis. Therefore, E-cadherin has become one of the important indicators for the prognosis assessment of nasopharyngeal carcinoma.

[0075] The experimental grouping was the same as that of Example 2. Total cell protein was extracted with RIPA lysis buffer, and the protein concentration was determined by the BCA method and then subjected to SDS-polyacrylamide gel electrophoresis. The protein was transferred to a PVDF membrane by a semi-dry method and blocked with 5% skim milk powder for 1 h. A primary antibody diluted with 5% skim milk powder was added according to the target protein to be detected, and the membrane was incubated at 4°C overnight. After washing three times with TBST, a secondary antibody diluted with 5% skim milk powder was added and incubated at room temperature with shaking for 2 h. After washing three times with TBST, the membrane was developed with ECL chemiluminescent solution in a chemiluminescent imager.

[0076] The total gray value of the protein bands was analyzed using Image J software to quantify the protein expression level of the gene. In order to confirm the same protein loading, GAPDH was used as an internal control in this study.

[0077] Compared with the untreated NC group, the experimental group showed significant biological effects after LUTE intervention. Specifically, LUTE not only effectively reduced the expression level of IL-6, a key inflammatory factor, but also significantly inhibited the protein content of p-JAK and p-STAT3, the phosphorylated forms of JAK and STAT3. This result suggests that LUTE may inhibit a series of downstream EMT-related gene expression changes by blocking the activation of the IL-6 / JAK / STAT3 signaling pathway; LUTE intervention significantly upregulated the expression of E-cadherin, an important intercellular adhesion molecule, whose upregulation is usually associated with the maintenance of epithelial cell characteristics and the reversal of EMT. In contrast, N-cadherin (neural cadherin), as a landmark molecule in the EMT process, had a significantly reduced protein level after LUTE treatment, which further confirmed the inhibitory effect of LUTE on the EMT process of NPC cells.

[0078] In summary, LUTE plays an important inhibitory role in the progression of NPC by regulating the IL-6 / JAK / STAT3 signaling pathway, possibly by inhibiting the expression changes of EMT-related molecules, such as reducing N-cadherin and upregulating E-cadherin.

[0079] The above description is only by way of illustration of certain exemplary embodiments of the present invention. It is undoubted that those skilled in the art can modify the described embodiments in various ways without departing from the spirit and scope of the present invention. Therefore, the above drawings and descriptions are illustrative in nature and should not be construed as limiting the scope of protection of the claims of the present invention.

Claims

1. Use of luteolin or a pharmaceutically acceptable salt thereof in the preparation of an anti-tumor metastasis drug, characterized in that: The structural formula of luteolin is as follows: The tumor is nasopharyngeal carcinoma.

2. The use according to claim 1, characterized in that: The luteolin or a pharmaceutically acceptable salt thereof is added with pharmaceutical excipients to prepare a preparation.

3. The use according to claim 2, characterized in that: The pharmaceutical excipients include one or more of diluents, excipients, fillers, adhesives, wetting agents, disintegrants, absorption promoters, surfactants, adsorption carriers, lubricants, and other excipients.

4. The use according to claim 2, characterized in that: The preparation is in the form of tablets, capsules, oral liquid, injection, lyophilized injection or powder injection.

5. The use according to claim 1, characterized in that: The luteolin or a pharmaceutically acceptable salt thereof inhibits the metastasis of nasopharyngeal carcinoma by targeting the IL-6 / JAK / STAT3 signaling pathway.

Images